Amyloids are protein aggregates that form fibrous deposits of proteins mainly having a cross-beta sheet secondary structure, which exhibit birefringence or fluorescence when stained with amyloid-specific dyes such as Congo red and thioflavin T and are insoluble in aqueous solutions (Murphy, R. M., Annu. Rev. Biomed. Eng., 4: 155, 2002). Basically, the amyloids are formed as a result of abnormal folding which leads to change in secondary and tertiary structures without change in the primary structure of proteins. The amyloid deposits induce tissue damage. The amyloids are associated with many diseases including Alzheimer's disease, prion-related encephalopathy, spongiform encephalopathy, Parkinson's disease, primary systemic amyloidosis, type 2 diabetes, familial amyloidosis and light-chain amyloidosis.
The amyloids are studied extensively only recently and there have been consistent researches on the abnormal folding of amyloid proteins and their cytotoxicity in order to elucidate the relationship between the deposition of amyloid proteins and neurodegenerative diseases. However, drugs for treating such diseases as Alzheimer's disease or prion disease have not been developed yet.
The existing drug development method is not applicable to the development of drugs for treating the amyloid-associated diseases caused by protein misfolding because of the absence of distinct recognition sites or binding pockets in amyloid proteins.
Although inhibitors have been developed based on the mechanisms of amyloid aggregation, e.g., increase of amyloid beta by SUMO1 (patent document 1), these methods are effective for single molecular species only.
The inventors of the present disclosure have made efforts to develop an inhibitor of protein misfolding leading to various amyloid aggregates or prions by using a self-assembled peptide nanostructure and have completed the present disclosure.